Tissue-to-tissue adhesions are attachments between tissues, organs, or other anatomical structures which are normally separate from one another. These adhesions are typically composed of fibrous bands of scar-like tissue which may form as a result of trauma, surgery, infection or other stimulus. Postsurgical adhesions resulting from abdominal, gynecological, or spinal surgeries are common and cause pain and other complications, and in some cases may require a second surgery to remove the adhesions. Various adhesion barriers have been developed to prevent or minimize the formation of these undesired tissue-to-tissue adhesions, but these barriers are either not very effective or are difficult to use. For example, preformed film barrier materials are fairly efficacious, but are difficult to handle by the surgeon. Hydrogels formed in situ by the reaction of two or more hydrogel precursors are easy to apply to the site, but these hydrogels have not proven to be very effective in preventing adhesions. Therefore, there is a need for more effective treatments for preventing undesired tissue-to-tissue adhesions caused by trauma, surgery, infection, or other stimulus, which are easy to use.
One type of hydrogel composition for inhibiting tissue adhesions is formed by reacting a carboxymethyldextran derivatized to contain hydrazide groups with a carboxymethylcellulose oxidized to contain aldehyde groups (Yeo et al., U.S. Patent Application Publication No. 2008/0069857). The hydrazide groups of the derivatized carboxymethyldextran react with the aldehyde groups of the oxidized carboxymethylcellulose to form a crosslinked hydrogel coating on the tissue. This hydrogel has been shown to be very effective in preventing post-surgical adhesions in a rabbit model, but it is very long-lasting, which may limit its clinical utility. Ideally, an adhesion prevention composition should not persist at the site once the healing process has begun, typically not longer than 1 to 3 weeks.
The problem to be solved therefore is to provide a tissue coating which is effective in preventing undesired tissue-to-tissue adhesions and which produces a hydrogel that degrades quickly, so that it does not interfere with the healing process.